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Alcohol and sepsis inhibit the expression of milk fat globule epidermal growth factor-factor VIII (MFG-E8), a glycoprotein essential for optimal efferocytosis, resulting in the release of proinflammatory molecules and increased sepsis severity. We previously reported that recombinant mouse (rm) MFG-E8 attenuates sepsis-induced organ injury in rats with acute alcohol intoxication. In order to develop a therapy that can be safely used in humans, we have produced recombinant human (rh) MFG-E8 and evaluated its efficacy to ameliorate sepsis after acute exposure to alcohol.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We induced acute alcohol intoxication with a bolus injection of alcohol (1.75\u2009g\/kg BW) followed by an intravenous infusion of 300\u2009mg\/kg\/h alcohol for 10\u2009h. Sepsis was then induced by cecal ligation and puncture (CLP). At -10, 0, and 10\u2009h relative to CLP, rats received MFG-E8 or vehicle (albumin) intravenously. Animals were euthanized at 20\u2009h after CLP for blood and tissue collection. Additional groups of animals were used for a survival study.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Compared to vehicle, rhMFG-E8 treatment ameliorated blood levels of proinflammatory cytokines (% improvement: TNF-\u03b1 49.8%, IL-6 34.7%) and endotoxin (61.7%), as well as of transaminases (AST 36.2%, ALT 40.1%) and lactate (18.4%). Rats treated with rhMFG-E8 also had a significant histological attenuation of the acute lung injury, as well as a reduction in the number of apoptotic cells in the thymus (43.4%) and cleaved caspase 3 (38.7%) in the spleen. In addition, rhMFG-E8 improved the 10-day sepsis survival rate from 45 to 80%<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>rhMFG-E8 significantly ameliorated sepsis in rats with acute alcohol exposure, demonstrating rhMFG-E8\u2019s potential to be developed as an effective therapy for sepsis in alcohol abusers.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s10020-019-0118-x","type":"journal-article","created":{"date-parts":[[2019,11,20]],"date-time":"2019-11-20T14:02:57Z","timestamp":1574258577000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Recombinant human milk fat globule-EGF factor VIII (rhMFG-E8) as a therapy for sepsis after acute exposure to alcohol"],"prefix":"10.1186","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1646-3814","authenticated-orcid":false,"given":"Wayne W.","family":"Chaung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Brenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Ting","family":"Yen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahendar L.","family":"Ochani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asha","family":"Jacob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,20]]},"reference":[{"key":"118_CR1","doi-asserted-by":"publisher","first-page":"e46540","DOI":"10.1371\/journal.pone.0046540","volume":"7","author":"MA Ajakaiye","year":"2012","unstructured":"Ajakaiye MA, Jacob A, Wu R, Yang WL, Nicastro J, Coppa GF, Wang P. 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